The long term goal of the proposed research is to elucidate the manner in which anesthesia alters metabolism, circulation and respiration and therefore occasions special considerations prior to, during and after clinical applications. More specifically we propose to determine the individual organ contributions to the whole body changes in oxygen uptake during anesthesia with the parenteral agent thiopental and the mechanisms involved, as we have previously accomplished for volatile anesthetic agents. We propose to determine the effects of thiopental on skeletal muscle metabolism and blood flow and to determine the time course of muscle supersensitivity and potassium efflux with paraplegia. A major effort will be made to determine the role of sympathetic hyperactivity and environmental factors in producing signs of malignant hyperthermia in stress susceptible swine in the absence of anesthetic agents. We further propose to examine potential enzyme deficiencies and the effects of thiopental and of non-depolarizing relaxants in modifying malignant hyperthermia. We propose to determine the efficacy of caffeine, halothane, and halothane-caffeine contractures in skeletal muscle biopsies in diagnosing susceptibility in swine and to continue evaluation of these in humans as a part of our role as a diagnostic center for malignant hyperthermia.